Plasma volume changes in middle-aged male and female subjects during marathon running

Circulatory fluid shifts were studied in middle-aged runners (6 males and 5 females, ages 32-58 yr) during a 42.2-km marathon race run in mild weather (dry-bulb temperature = 17.5-20.4 degrees C). Running times for the subjects were 3:12-4:40 (mean values were 3:34 for males and 4:10 for females). Venous blood samples were taken without stasis in all subjects seated at rest before the start of the race and within 3 min of finishing; eight of the subjects also paused for samples at 6 and 27 km during the race. At 6 km, body weight loss averaged less than 1%, whereas plasma volume (PV) had decreased by 6.5% in male subjects and 8.6% in female subjects. By the end of the race, hypohydration had reached 3.2% in male subjects and 2.9% in female subjects, but PV in both groups remained stable. Sweat rates during the race averaged 545 and 429 g X m-2 X h-1 for male and female subjects, respectively, with ad lib. water intake replacing 21-72% of fluid loss. Increases in plasma protein concentration throughout the race reflected the observed initial decrease in PV. The interpretation of PV responses to exercise and/or hypohydration is critically dependent on selection of base-line conditions; we were able to control for posture-exercise effects by treating the early exercise (6 km) sample as the base line for examining the effects of later fluid loss. Under these conditions, the vascular compartment resisted volume depletion. The ability to maintain stable PV can be explained in part by relationships among oncotic and hydrostatic pressures in the intra- and extravascular fluid compartments.     

The xylem sap of maple (Acer platanoides) trees--sap obtained by a novel method shows changes with season and height

Xylem sap of log pieces of maple trees was collected by a novelpressure/decompression method developed recently for the mechanicaldrying of timber. Seasonal changes and spatial distributionsof the osmotic potential, the pH and the concentrations of majorsolutes and of the plant stress-hormone abscisic acid (ABA)were investigated. Sucrose and quebrachitol were the main components of the xylemsap. The sucrose concentration varied between 10 mM and 25 mMduring the winter months and declined to a minimum during theperiod of bud burst. Quebrachitol was found in concentrationsof up to 7 mM with a high variability throughout the year. Highconcentrations of ABA were measured during the summer seasonand in mid-winter. Rainfall caused an increase of ABA in somesamples. The osmotic potential of the xylem sap increased with the heightof the collection site. The pH of the sap decreased by approximatelyone unit between the base of the trunk and the crown. The increaseof the osmotic potential was mainly due to sucrose, quebrachitoland potassium. Malate contributed to the decrease of the pH.ABA of the xylem sap increased with decreasing moisture contentof the wood. Key words: Pressure/decompression method, xylem sap, abscisic acid, sucrose, quebrachitol, Acer platanoides     

Polymorphism of the tumor necrosis factor beta gene in systemic lupus erythematosus: TNFB-MHC haplotypes

We investigated the Nco I restriction fragment length polymorphism (RFLP) of the tumor necrosis factor beta (TNFB) gene in 173 patients with systemic lupus erythematosus (SLE), 192 unrelated healthy controls, and eleven panel families, all of German origin. The phenotype frequency of the TNFB*1 allele was significantly increased in patients compared to controls (63.6% vs 47.1%, RR = 1.96, p <0.002). The results of a two-point haplotype statistical analysis between TNFB and HLA alleles show that there is linkage disequilibrium between TNFB*1 and HLA-A1, Cw7, B8, DR3, DQ2, and C4A DE. The frequency of TNFB*1 was compared in SLE patients and controls in the presence or absence of each of these alleles. TNFB*1 is increased in patients over controls only in the presence of the mentioned alleles. Therefore, the whole haplotype A1, Cw7, B8, TNFB*1, C4A DE, DR3, DQ2 is increased in patients and it cannot be determined which of the genes carried by this haplotype is responsible for the susceptibility to SLE. In addition, two-locus associations were analyzed in 192 unrelated healthy controls for TNFB and class I alleles typed by serology, and for TNFB and class II alleles typed by polymerase chain reaction/oligonucleotide probes. We found positive linkage disequilibrium between TNFB*1 and the following alleles: HLA-A24, HLA-B8, DRB1*0301, DRB1*1104, DRB1*1302, DQA1*0501, DQB1*0201, DQB1*0604, and DPB1*0101. TNFB*2 is associated with HLA-B7, DRB1*1501, and DQB1*0602.This study was supported by grants from the Federal Ministry of Research and Technology (BMFT/DFVLR, 01 VM 8608/9), the German Academic Exchange Service (DAAD, 322/501/014/0), and SFB (217).This work is part of the doctoral thesis of M. P. Bettinotti.     

Prevention and therapy of experimental autoimmune neuritis by an antibody against T cell receptors-alpha/beta.

The mAb R73 directed to the TCR-alpha/beta of rat lymphocytes was tested for its therapeutic potential during the effector phase of experimental autoimmune neuritis (EAN) in Lewis rats. EAN can be actively induced by immunization with bovine peripheral nerve myelin, bovine P2 protein, or a peptide containing its neuritogenic epitope and serves as a model of the human Guilain-Barré syndrome. Adoptive transfer of activated P2-specific T lymphocytes also produces the monophasic disease (AT-EAN) characterized by inflammation and demyelination of peripheral nerves and highlights the central role of T lymphocytes in the pathogenesis of EAN. A single administration of the mAb R73 immediately after injection of activated P2-specific T line cells completely prevented the development of clinical and electrophysiologic signs of EAN in most animals and greatly alleviated the disease in the others. In further experiments mAb R73 was applied after the appearance of first clinical signs of EAN actively induced by immunization with a neuritogenic peptide or bovine peripheral nerve myelin. In both cases the anti-TCR-alpha/beta mAb reversed clinical signs of EAN and prevented the development of peripheral nerve dysfunction. In vivo and in vitro data suggest that impairment of Ag recognition and T cell function by occupancy of the TCR and R73-induced TCR-modulation rather than depletion of TCR-alpha/beta-bearing lymphocytes is the decisive mechanism underlying suppression of EAN that is apparent already within 48 h of the first R73 injection.     

Chromosomal constitution of nucleolus-associated chromatin in man

Summary Use of specific stains permits analysis of the frequency of nucleolus-associated heterochromatin in chromosomes 1 and 9 from human fibroblasts. In 81% of interphase nuclei the heterochromatic segment of both No. 1 chromosomes is associated with the nucleolus, while in 19% only one heterochromatic segment shows such an association with the other occupying a random position in the nucleoplasm. The nucleolar association of chromosome 9 heterochromatin is less constant: in 42.3% of the nuclei both segments are associated with the nucleolus, in 39% of the nuclei only one heterochromatic segment presents such an association, and in 18.7% neither of the two heterochromatic segments is in nucleolar association. In 6% of the cells, one or two chromosome 9 heterochromatic segments are in contact with the nuclear membrane.In situ hybridization using tritium-labeled 28S and 18S RNA shows that in the interphase nucleus the acrocentric short arms, carriers of ribosomal cistrons, are associated with the nucleolus.These observations demonstrate the complexity of the nucleolus-associated chromatin which, in addition to segments of chromosomes 1, 9, 13, 14, 15, 21 and 22, may include the Y chromosome. They also confirm that the nucleolus constitutes one of the orientation points determining the relative localization of chromosomes in the interphase nucleus.     

Mitogen-activated protein kinase-activated protein kinase 2-deficient mice show increased susceptibility to Listeria monocytogenes infection

Mitogen-activated protein kinase-activated protein kinase 2 (MK2) is one of several kinases activated through direct phosphorylation by p38 mitogen-activated protein kinase. MK2 regulates LPS-induced TNF mRNA translation, and targeted mutation of the MK2 gene renders mice more resistant to D-galactosamine plus LPS-induced liver damage. In the present study, we investigated the role of MK2 in immune defense against Listeria monocytogenes infection. MK2-deficient mice displayed diminished resistance to L. monocytogenes due to impaired control of bacterial growth. The increase in bacterial load in MK2(-/-) mice was associated with normal levels of IL-1 beta, IL-6, and IFN-gamma, whereas TNF production was strongly attenuated. In line, MK2-deficient bone marrow-derived macrophages showed impaired release of TNF, but not of IL-1 beta, in response to various bacterial stimuli in addition to decreased phagocytosis of fluorescence-labeled bacteria. Furthermore, spleen cells from MK2(-/-) mice displayed diminished IFN-gamma synthesis after stimulation with L. monocytogenes. In contrast, MK2 deficiency had no effect on macrophage generation of NO or on oxidative burst activity in response to L. moocytogenes. These results indicate an essential role of MK2 in host defense against intracellular bacteria probably via regulation of TNF and IFN-gamma production required for activation of antibacterial effector mechanisms.